Small molecule chemotherapeutic drugs such as doxorubicin (DOX) have been employed in cancer therapy (Dimarco et al., 1969). However, their effectiveness is hampered by specific and systemic toxicity (Vonhoff et al., 1979). With limited success, prodrugs have been shown to help reduce systemic toxicity (Rooseboom et al., 2004). To increase efficacy and overcome the problem of systemic toxicity, drug carriers or vehicles, including nanomaterials, have been developed to deliver drug molecules to tumors (Gabizon et al., 1994; Arora et al., 2012; Qin et al., 2011). Drugs delivered in these carriers must be released upon reaching tumor sites, either through internal/natural or external triggering mechanisms. Natural triggering has the advantage of using the tumor itself to trigger the release (Dhar et al., 2009). External triggering such as microwaves, ultrasound, light and especially near IR light, and magnetic fields have been explored as the trigger for the release of drug molecules (Schroeder et al., 2009; West et al., 2007; Liu et al., 2011; Wang et al, 2011).
X-rays can potentially become a successful external triggering tool to release drugs from nanomaterial or nanoparticle drug carriers (NDC). Because X-rays are highly penetrating and have been used clinically in diagnosis and treatment of tumor, X-ray triggered release mechanisms may find immediate clinical applications. Demonstrations of X-ray triggered, controlled release of drugs from carriers or vehicles in pure water have been reported (O'Brien et al., 2001). However, no release has been shown in vitro or in vivo, such as in living cells, which are nearly hundred times more radiation resistive due to the presence of radical scavengers. Other triggering modalities such as infrared light and microwave have been used with other types of nanomaterial-based drug delivery vehicles. However, they all suffer certain shortcomings such as lack of location precision or shallow penetration depths. Prodrugs have been developed in the past, in which the drug portion can be cleaved from the base molecules upon X-ray irradiation. However, these prodrugs still retain systematic toxicity because they tend to be deposited in many places unintended for delivery.
Thus, there exists a need for a drug delivery device that can deliver a prodrug to a target cellular location and controllably release the drug at that target cellular location.